{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T22:24:40Z","timestamp":1793053480440,"version":"4.5.0"},"reference-count":36,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2020,11,4]],"date-time":"2020-11-04T00:00:00Z","timestamp":1604448000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    We present a study to evaluate the feasibility and clinical utility of amplicon\u2010based Oncomine Pan\u2010Cancer cell\u2010free assay to detect circulating tumor DNA (ctDNA) in patients with early or advanced breast cancer. In this study, 109 early and metastatic breast cancer patients were recruited before the initiation of treatment. ctDNA mutation profiles were assessed through unique molecular tagging (UMT) and ultradeep next generation sequencing (NGS). For patients with mutations, DNA from corresponding white blood cells (WBC) was sequenced to exclude variants of clonal\u2010hematopoietic (CH) origin. UMT targeted sequencing from plasma of 109 patients achieved a median total coverage of 55\u00a0498X and a median molecular coverage of 4187X. Among 53 ctDNA positive samples, 38% were mutation positive by WBC sequencing, indicating potentially false\u2010positive results contributed by CH origin. Prevalence of CH\u2010related mutations was associated with age (\n                    <jats:italic>P\u00a0<\/jats:italic>\n                    =\u00a07.51\u00a0\u00d7\u00a010\n                    <jats:sup>\u22124<\/jats:sup>\n                    ). After exclusion of CH mutations, ctDNA detection rates were 37% for local or locally advanced breast cancer (stage I\u2010III) and 81% for metastatic or recurrent breast cancer. The ctDNA detection rate correlated with disease stage (\n                    <jats:italic>P<\/jats:italic>\n                    \u00a0=\u00a02.60\u00a0\u00d7\u00a010\n                    <jats:sup>\u22124<\/jats:sup>\n                    ), nodal spread (\n                    <jats:italic>P<\/jats:italic>\n                    \u00a0=\u00a06.49\u00a0\u00d7\u00a010\n                    <jats:sup>\u22123<\/jats:sup>\n                    ) and the status of distant metastases (\n                    <jats:italic>P<\/jats:italic>\n                    \u00a0=\u00a05.00\u00a0\u00d7\u00a010\n                    <jats:sup>\u22124<\/jats:sup>\n                    ). ctDNA variants were detected mostly in\n                    <jats:italic>TP53<\/jats:italic>\n                    ,\n                    <jats:italic>PIK3CA<\/jats:italic>\n                    and\n                    <jats:italic>AKT1<\/jats:italic>\n                    genes, with variants showing therapeutic relevance. This pilot study endorses the use of targeted NGS for non\u2010invasive molecular profiling of breast cancer. Paired sequencing of plasma ctDNA and WBC should be implemented to improve accurate interpretation of liquid biopsy.\n                  <\/jats:p>","DOI":"10.1111\/cas.14697","type":"journal-article","created":{"date-parts":[[2020,10,19]],"date-time":"2020-10-19T14:41:57Z","timestamp":1603118517000},"page":"454-464","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Ultradeep targeted sequencing of circulating tumor DNA in plasma of early and advanced breast cancer"],"prefix":"10.1111","volume":"112","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4667-3561","authenticated-orcid":false,"given":"Yoon Ming","family":"Chin","sequence":"first","affiliation":[{"name":"Cancer Precision Medicine Center The Cancer Institute Japanese Foundation for Cancer Research Tokyo Japan"},{"name":"Cancer Precision Medicine Inc. Kawasaki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoko","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Breast Oncology Center Cancer Institute Hospital Japanese Foundation for Cancer Research Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8707-4592","authenticated-orcid":false,"given":"Hiu Ting","family":"Chan","sequence":"additional","affiliation":[{"name":"Cancer Precision Medicine Center The Cancer Institute Japanese Foundation for Cancer Research Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masumi","family":"Otaki","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Cancer Institute Hospital Japanese Foundation for Cancer Research Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makoto","family":"Fujishima","sequence":"additional","affiliation":[{"name":"Department of Surgery Kuma Hospital Kobe Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoko","family":"Shibayama","sequence":"additional","affiliation":[{"name":"Breast Oncology Center Cancer Institute Hospital Japanese Foundation for Cancer Research Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshio","family":"Miki","sequence":"additional","affiliation":[{"name":"Department of Genetic Diagnosis The Cancer Institute Japanese Foundation for Cancer Research Tokyo Japan"},{"name":"Department of Molecular Genetics Medical Research Institute Tokyo Medical &amp; Dental University Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9080-9377","authenticated-orcid":false,"given":"Takayuki","family":"Ueno","sequence":"additional","affiliation":[{"name":"Breast Oncology Center Cancer Institute Hospital Japanese Foundation for Cancer Research Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuke","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Cancer Precision Medicine Center The Cancer Institute Japanese Foundation for Cancer Research Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2386-0698","authenticated-orcid":false,"given":"Siew\u2010Kee","family":"Low","sequence":"additional","affiliation":[{"name":"Cancer Precision Medicine Center The Cancer Institute Japanese Foundation for Cancer Research Tokyo 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